Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA.Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis.Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 +/- 13.5 (p < 0.001) for DAPSA and 1.21 +/- 0.97 (p < 0.001) for ASDAS-CRP. thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naive to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24.conclusions this is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months

Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas

BACKGROUND/AIMS: Fish oil supplementation can reduce cytokinetic anomalies in the flat rectal mucosa of patients with sporadic colorectal adenoma. This study attempted to identify an optimum dose for fish oil supplementation and evaluate the persistence of its effects during long-term administration. METHODS: In a double-blind study, 60 patients with sporadic adenomas received 2.5, 5.1, or 7.7 g of fish oil per day or placebo for 30 days. [3H]thymidine autoradiographic labeling indices were calculated in flat rectal mucosal biopsy specimens collected before and after supplementation. In a subsequent study, 15 patients with polyps received 2.5 g of fish oil per day. Proliferative parameters, mucosal fatty acids, and mucosal and plasma alpha-tocopherol levels were evaluated before, during, and after 6 months of supplementation. RESULTS: Mean proliferative indices and mucosal arachidonic acid levels decreased significantly (and to similar degrees) in all treated groups, whereas mucosal eicosapentaenoic and docosahexaenoic acid levels increased. Significantly reduced proliferation was observed only in patients with abnormal baseline patterns. These effects persisted during long-term, low-dose treatment. A transient reduction in mucosal (but not plasma) alpha-tocopherol levels was observed after 1 month of treatment. Side effects were insignificant. CONCLUSIONS: Low-dose fish oil supplementation has short-term and long-term normalizing effects on the abnormal rectal proliferation patterns associated with increased colon cancer risk

DNA ploidy pattern in human chronic liver diseases and hepatic nodular lesions. Flow cytometric analysis on echo‐guided needle liver biopsy

Background. Significantly elevated fractions of diploid hepatocytes and reduction in the polyploid populations have been reported in human and experimentally induced hepatocellular carcinomas (HCC). This study was conducted to determine how these changes are related to conditions that often precede HCC, such as chronic hepatitis, cirrhosis, and premalignant focal nodules in cirrhotic livers. Methods. Ultrasound‐guided needle biopsy specimens of the liver were obtained from patients with chronic hepatitis, cirrhosis, or ultrasonographically diagnosed nodules within cirrhotic livers; biopsy specimens also were taken from patients without hepatic disease. DNA flow cytometry was performed on isolated nuclei to determine the percentages of diploid, tetraploid, and octaploid hepatocytes; the S‐phase fraction for each diploid peak and the diploid/polyploid (tetraploid + octaploid) ratio also were calculated. Part of each specimen was reserved for evaluation of hepatocyte binuclearity. Results. Chronically hepatitic (18 patients) and cirrhotic (18 patients) livers showed significantly increased diploid/polyploid ratios, with respect to normal livers, that were significantly correlated with decreases in hepatocyte binuclearity. This trend was even more marked in euploid nodules (4 premalignant and 5 malignant), in which the S‐phase fractions were significantly higher than those of normal liver; aneuploidy was found in 6 of 11 malignant and 2 of 6 premalignant nodules. Conclusions. Ploidy reductions noted in HCC also are present in chronic hepatitis and cirrhosis and may be related to tissue regeneration. Marked diploidization characterizes nodular lesions and may predispose them to more severe alterations, such as aneuploidy. Copyright © 1994 American Cancer Societ

Effect of ω-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer

The effects of 12 weeks of ω-3 fatty acid supplementation on rectal mucosal proliferation were assessed with [3H]thymidine autoradiography in a double-blind, placebo-controlled study of 20 patients with sporadic adenomatous colorectal polyps. In the group of 10 that received fish oil containing eicosapentaenoic acid (4.1 g/day) and docosahexaenoic acid (3.6 g/day), the mean percentage of replicative "S"-phase cells in the upper part of colonic crypts (considered a reliable marker of colon cancer risk) significantly dropped from the baseline level after only 2 weeks of treatment and remained lower throughout the study period; no change in upper-crypt labeling was observed in the 10 placebo patients. Rectal mucosal eicosapentaenoic acid content increased in fish oil patients, whereas arachidonic acid levels decreased. The fish oil-induced kinetic changes represent contraction of the proliferative compartment to the levels of a low-risk population and may be related to ω-3 fatty acid effects on the arachidonic prostaglandin pathway. In this short-term trial, fish oil appeared to exert a rapid effect that may protect high-risk subjects from colon cancer. © 1992

Dose-response effect of baclofen in reducing daily alcohol intake in alcohol dependence: Secondary analysis of a randomized, double-blind, placebo-controlled trial

To explore the effect of baclofen in a dose of 20 mg three times per day, compared with the already studied dose of 10 mg three times per day, in the treatment of alcohol dependence. Methods: We present a secondary analysis of a 12-week double-blind, placebo-controlled, randomized clinical trial with two doses of baclofen, specifically 10 mg t.i.d. and 20 mg t.i.d. Out of 94 subjects consecutively screened, 42 were randomized into the study. Fourteen of the 42 patients were randomly allocated to placebo, 14 to the group treated with baclofen 10 mg t.i.d. (B10 mg) and 14 to the group treated with baclofen 20 mg t.i.d. (B20 mg). Results: Compared with patients allocated to placebo, patients allocated to the B10 mg group had a 53% reduction in the number of drinks per day (P < 0.0001) and patients allocated to the B20 mg group had a 68% reduction in the number of drinks per day (P < 0.0001), with respect to the number of drinks per day during the 28 days before randomization. The effect of baclofen 20 mg t.i.d. was greater than that of baclofen 10 mg t.i.d. (P = 0.0214, Wald test) showing a dose-effect relationship. Both doses of baclofen were well tolerated. Conclusion: This is provisional evidence of a dose-response effect for baclofen in the treatment of alcohol dependence